Potential to Enhance Large Scale Molecular Assessments of Skin Photoaging through Virtual Inference of Spatial Transcriptomics from Routine Staining.

The advent of spatial transcriptomics technologies has heralded a renaissance in research to advance our understanding of the spatial cellular and transcriptional heterogeneity within tissues. Spatial transcriptomics allows investigation of the interplay between cells, molecular pathways, and the surrounding tissue architecture and can help elucidate developmental trajectories, disease pathogenesis, and various niches in the tumor microenvironment. Photoaging is the histological and molecular skin damage resulting from chronic/acute sun exposure and is a major risk factor for skin cancer. Spatial transcriptomics technologies hold promise for improving the reliability of evaluating photoaging and developing new therapeutics. Challenges to current methods include limited focus on dermal elastosis variations and reliance on self-reported measures, which can introduce subjectivity and inconsistency. Spatial transcriptomics offers an opportunity to assess photoaging objectively and reproducibly in studies of carcinogenesis and discern the effectiveness of therapies that intervene in photoaging and preventing cancer. Evaluation of distinct histological architectures using highly-multiplexed spatial technologies can identify specific cell lineages that have been understudied due to their location beyond the depth of UV penetration. However, the cost and interpatient variability using state-of-the-art assays such as the 10x Genomics Spatial Transcriptomics assays limits the scope and scale of large-scale molecular epidemiologic studies. Here, we investigate the inference of spatial transcriptomics information from routine hematoxylin and eosin-stained (H&E) tissue slides. We employed the Visium CytAssist spatial transcriptomics assay to analyze over 18,000 genes at a 50-micron resolution for four patients from a cohort of 261 skin specimens collected adjacent to surgical resection sites for basal cell and squamous cell keratinocyte tumors. The spatial transcriptomics data was co-registered with 40x resolution whole slide imaging (WSI) information. We developed machine learning models that achieved a macro-averaged median AUC and F1 score of 0.80 and 0.61 and Spearman coefficient of 0.60 in inferring transcriptomic profiles across the slides, and accurately captured biological pathways across various tissue architectures.

Machine learning-based prediction of low-value care for hospitalized patients.

Objective: Low-value care (i.e., costly health care treatments that provide little or no benefit) is an ongoing problem in United States hospitals. Traditional strategies for reducing low-value care are only moderately successful. Informed by behavioral science principles, we sought to use machine learning to inform a targeted prompting system that suggests preferred alternative treatments at the point of care but before clinicians have made a decision. Methods: We used intravenous administration of albumin for fluid resuscitation in intensive care unit (ICU) patients as an exemplar of low-value care practice, identified using the electronic health record of a multi-hospital health system. We divided all ICU episodes into 4-h periods and defined a set of relevant clinical features at the period level. We then developed two machine learning models: a single-stage model that directly predicts if a patient will receive albumin in the next period; and a two-stage model that first predicts if any resuscitation fluid will be administered and then predicts albumin only among the patients with a high probability of fluid use. Results: We examined 87,489 ICU episodes divided into approximately 1.5 million 4-h periods. The area under the receiver operating characteristic curve was 0.86 for both prediction models. The positive predictive value was 0.21 (95% confidence interval: 0.20, 0.23) for the single-stage model and 0.22 (0.20, 0.23) for the two-stage model. Applying either model in a targeted prompting system could prevent 10% of albumin administrations, with an attending physician receiving one prompt every 4.2 days of ICU service. Conclusion: Prediction of low-value care is feasible and could enable a point-of-care, targeted prompting system that offers suggestions ahead of the moment of need before clinicians have already decided. A two-stage approach does not improve performance but does interject new levers for the calibration of such a system.